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Background: Triple negative breast cancer (TNBC) has the worst prognosis amongst all subtypes. Studies have shown that the achievement of pathologic complete response in the breast and axilla correlates with improved survival. The aim of this study was to identify clinical or pathological features of real-life TNBC patients with a higher risk of early relapse. Materials and methods: Single-centre retrospective analysis of 127 women with TNBC, stage II-III, submitted to neoadjuvant treatment and surgery between January 2016 and 2020. Multivariate Cox regression analysis for disease free survival (DFS) at 2 years was performed and statistically significant variables were computed into a prognostic model for early relapse. Results: After 29 months of median follow-up, 105 patients (82.7%) were alive and, in total, 38 patients (29.9%) experienced recurrence. The 2-year DFS was 73% (95% CI: 21.3-22.7). In multivariate analysis, being submitted to neoadjuvant radiotherapy [HR 2.8 (95% CI: 1.2-6.4), p = 0.017] and not achieving pathologic complete response [HR 0.3 (95% CI: 0.1-1.7), p = 0.011] were associated with higher risk of recurrence. In our prognostic model, the presence of at least one of these variables defined a subgroup of patients with a worse 2-year DFS than those without these features (59% vs. 90%, p < 0.001, respectively). Conclusions: In this real-life non-metastatic TNBC cohort, neoadjuvant radiotherapy (performed due to insufficient clinical response to neoadjuvant chemotherapy or significant toxicity) impacted as an independent prognostic factor for relapse along with the absence of pathologic complete response identifying a subgroup of higher risk patients for early relapse that might merit a closer follow-up. [ABSTRACT FROM AUTHOR]

En esta investigación se estudió la influencia de la composición lipídica en la capacidad inmunomoduladora de las vesículas liposomales. Para ello se emplearon liposomas de fosfatidilcolina (PC), de diferente naturaleza, y colesterol, como adyuvantes del factor de crecimiento epidérmico humano recombinante (EGFhr), conjugado o no a la proteína transportadora P64k de Neisseria meningitidis, y liposomas de dipalmitoilfosfatidilcolina (DPPC), que contenían o no colesterol para encapsular alergenos (maDer s) y sticholisina II (StII), una proteína formadora de poros de Stichodactyla helianthus. Al estudiar la respuesta inmune anti-EGFhr, se evidenció la inducción de títulos de anticuerpos elevados, la promoción de IgG2a e IgG2b, las respuestas de hipersensibilidad retardada y la linfoproliferación, así como un incremento en la supervivencia frente al tumor ascítico de Ehrlich de los ratones inmunizados, aun en ausencia de la P64k. Esta respuesta fue superior para los liposomas constituidos por fosfatidilcolinas saturadas, en comparación con una insaturada (soya: sPC) y con la alúmina. También se demostró que la respuesta humoral alergeno-específica dependió de la composición lipídica liposomal y de la presencia de StII. En los ratones inmunizados con los liposomas que contenían colesterol no se observó respuesta alérgica. Estas preparaciones indujeron elevadas relaciones IgG2a/IgG1, lo que sugiere un patrón Th1. Esta constituye la primera evidencia del efecto inmunomodulador de StII. [ABSTRACT FROM AUTHOR]

We studied the influence of lipid composition on the immunomodulatory capacity of liposomal vesicles. Liposomes composed of different phosphatidylcholines (PC) and cholesterol were assayed as adjuvants for rhEGF conjugated or not to P64k from Neisseria meningitidis, and dipalmitoylphosphatidylcholine (DPPC) liposomes with or without cholesterol were tested for the encapsulation of allergens (maDer s) and sticholysin II (StII), a pore-forming protein from Stichodactyla helianthus. The immunization of mice under these conditions produced high antibody titers against rhEGF even in the absence of P64k, composed of IgG2a and IgG2b subclasses, a delayed hypersensitivity response, lymphoproliferation, and increased survival rates in mice challenged with Ehrlich's ascitic tumor. This immune response was superior when employing saturated phosphatidylcholine liposomes, as compared to unsaturated liposomes (soy bean: sPC) or Alum. Additionally, the humoral allergen-specific immune response depended on the liposomal lipid composition and on the presence of StII. No allergic responses were detected in mice immunized with cholesterol-containing liposomes; and these preparations induced the highest IgG2a/IgG1 ratio, suggesting the presence of a Th1 response pattern. These findings constitute the first reported evidence on immunomodulatory effects of StII. [ABSTRACT FROM AUTHOR]

Neuroendocrine carcinoma of the cervix (NECC) is a rare and extremely aggressive disease. Treatment options are scarce (mainly consisting of platinum-based chemotherapy combinations), and randomized controlled trials are lacking, leading to a very poor prognosis. It is prone to early metastasis, often with more than one affected site at diagnosis. The lung, liver, brain, and bone are the most frequent sites. We present the case of a 33-year-old female patient with no significant medical history. Postcoital bleeding led to the diagnosis of human papillomavirus (HPV)-related NECC after a tissue biopsy of a cervical mass. Disease staging showed suspected metastasis on the breast, pancreas, and ovaries, each of which is very rarely described in the literature. Both the breast and ovarian metastases were histologically confirmed through biopsy, while pancreatic metastases were deemed highly likely based on radiological findings. The patient was started on first-line chemotherapy with significant toxicities and rapid disease progression and is currently on third-line chemotherapy treatment. To our knowledge, this is the first reported case of these very rare sites of metastasis from NECC being present simultaneously, highlighting the complexity of this challenging entity., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Santos et al.)